Transient effects of levamisole on Brugia malayi microfilariae (original) (raw)

Abstract

Levamisole is an anthelmintic drug that acts by activating nicotinic acetylcholine receptors at the nematode neuromuscular junction and causing paralysis. We measured the in vitro effects of levamisole on the motility of Brugia malayi microfilariae; after 2 h incubation the apparent IC50 was 2.68 mM. Lower drug concentrations, such as 1 mM, caused an immediate total paralysis that lasted for up to 1 h, but was completely reversed by 2 h of incubation. The ‘recovered’ parasites were still completely susceptible to application of a second nicotinic agonist, pyrantel.

Fig. 1

References

• Bennett HM, Williamson SM, Walsh TK, Woods DJ, Wolstenholme AJ (2012) ACR-26: a novel nicotinic receptor subunit of parasitic nematodes. Mol Biochem Parasitol 183:151–157
  Article CAS PubMed Google Scholar
• Harrow ID, Gration AF (1985) Mode of action of the anthelmintics morantel, pyrantel and levamisole on muscle cell membrane of the nematode Ascaris suum. Pestic Sci 16:662–672
  Article CAS Google Scholar
• John PAS, Gordon H (2001) Agonists cause endocytosis of nicotinic acetylcholine receptors on cultured myotubes. J Neurobiol 49:212–223
  Article Google Scholar
• Jones AK, Sattelle DB (2004) Functional genomics of the nicotinic acetylcholine receptor gene family of the nematode, Caenorhabditis elegans. BioEssays 26:39–49
  Article CAS PubMed Google Scholar
• Li B-W, Rush AC, Weil GJ (2015) Expression of five acetylcholine receptor subunit genes in Brugia malayi adult worms. Int J Parasitol Drugs Drug Resist 5:100–109
  Article PubMed Central PubMed Google Scholar
• Marcellino C, Gut J, Lim KC, Singh R, McKerrow J, Sakanari J (2012) WormAssay: a novel computer application for whole-plate motion-based screening of macroscopic parasites. PLoS Negl Trop Dis 6:e1494
  Article PubMed Central PubMed Google Scholar
• Martin RJ (1997) Modes of action of anthelmintic drugs. Vet J 154:11–34
  Article CAS PubMed Google Scholar
• Qian H, Martin RJ, Robertson AP (2006) Pharmacology of N-, L-, and B-subtypes of nematode nAChR resolved at the single-channel level in Ascaris suum. FASEB J 20:E2108–E2116
  Article Google Scholar
• Robertson AP, Puttachary S, Martin RJ (2011) Single-channel recording from adult Brugia malayi. Invertebr Neurosci 11:53–57
  Article Google Scholar
• Robertson AP, Buxton SK, Martin RJ (2013) Whole-cell patch-clamp recording of nicotinic acetylcholine receptors in adult Brugia malayi muscle. Parasitol Int 62:616–618
  Article PubMed Central CAS PubMed Google Scholar
• Storey B, Marcellino C, Miller M, Maclean M, Mostafa E, Howell S et al (2014) Utilization of computer processed high definition video imaging for measuring motility of microscopic nematode stages on a quantitative scale: “The Worminator”. Int J Parasitol Drugs Drug Resist 4:233–243
  Article PubMed Central PubMed Google Scholar
• Taly A, Corringer P-J, Guedin D, Lestage P, Changeux J-P (2009) Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system. Nat Rev Drug Discov 8:733–750
  Article CAS PubMed Google Scholar
• Touroutine D, Fox RM, Von Stetina SE, Burdina A, Miller DM, Richmond JE (2005) acr-16 encodes an essential subunit of the levamisole-resistant nicotinic receptor at the Caenorhabditis elegans neuromuscular junction. J Biol Chem 280:27013–27021
  Article CAS PubMed Google Scholar
• Williamson SM, Walsh TK, Wolstenholme AJ (2007) The cys-loop ligand-gated ion channel gene family of Brugia malayi and Trichinella spiralis: a comparison with Caenorhabditis elegans. Invertebr Neurosci 7:219–226
  Article CAS Google Scholar
• Williamson SM, Robertson AP, Brown L, Williams T, Woods DJ, Martin RJ et al (2009) The nicotinic acetylcholine receptors of the parasitic nematode Ascaris suum: formation of two distinct drug targets by varying the relative expression levels of two subunits. PLoS Pathog 5:e1000517
  Article PubMed Central PubMed Google Scholar
• Zahner H, Schares G (1993) Experimental chemotherapy of filariasis—comparative-evaluation of the efficacy of filaricidal compounds in Mastomys coucha infected with Litomosoides carinii, Acanthocheilonema viteae, Brugia malayi and Brugia pahangi. Acta Trop 52:221–266
  Article CAS PubMed Google Scholar

Download references

Acknowledgments

This work was supported by funds from the Egyptian Cultural and Educational Bureau, Washington, DC, USA. We thank Dr Barbara Reaves for a critical reading of the manuscript.

Author information

Authors and Affiliations

1. Department of Infectious Diseases, University of Georgia, 501 D.W. Brooks Drive, Athens, GA, 30602, USA
   Eman Mostafa, Bob Storey & Adrian J. Wolstenholme
2. Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, USA
   Eman Mostafa & Adrian J. Wolstenholme
3. Department of Parasitology, Zagazig University, Zagazig, Egypt
   Eman Mostafa, Adel Mohammed Farghaly, Hany Abd El-Hai Afify & Afaf Abd El-Raouf Taha

Authors

1. Eman Mostafa
2. Bob Storey
3. Adel Mohammed Farghaly
4. Hany Abd El-Hai Afify
5. Afaf Abd El-Raouf Taha
6. Adrian J. Wolstenholme

Corresponding author

Correspondence toAdrian J. Wolstenholme.

Ethics declarations

Conflict of interest

None.

Rights and permissions

About this article

Cite this article

Mostafa, E., Storey, B., Farghaly, A.M. et al. Transient effects of levamisole on Brugia malayi microfilariae.Invert Neurosci 15, 5 (2015). https://doi.org/10.1007/s10158-015-0181-0

Download citation

• Received: 01 April 2015
• Accepted: 09 July 2015
• Published: 18 July 2015
• DOI: https://doi.org/10.1007/s10158-015-0181-0

Keywords